Analysis of the spatial-temporal evolution of Green and low carbon utilization efficiency of agricultural land in China and its influencing factors under the goal of carbon neutralization.

Agricultural land is the most basic input factor for agricultural production and an essential component of terrestrial ecosystems, which plays a vital role in achieving carbon neutrality. Giving full play to the carbon-neutral contribution of agricultural land is a crucial part of China's economic transformation and green development. It incorporates carbon and pollution emissions from agricultural land use into the unexpected outputs of the Green and Low-carbon Utilization Efficiency of Agricultural Land (GLUEAL) evaluation system. The study utilized several advanced analytical tools, including the super-efficient Slacks-Based Measure (SBM) model, Exploratory Spatial-Temporal Data Analysis (ESTDA) method, Geodetector, and Geographically and Temporally Weighted Regression (GTWR) model. The objective was to examine the spatial-temporal evolution of GLUEAL and identify the factors that influenced it in all 31 provinces of China from 2005 to 2020. The results show that: (1) The overall spatial-temporal evolution of GLUEAL showed an increasing trend, but the disparity between provinces and regions became wider. (2) Most provinces have not yet made significant spatial and temporal jumps. They have high spatial cohesion with specific "path-dependent" characteristics. (3) The Geodetector results reveal that the Number of Rural Labor Force with Higher Education (NRLFHE) and Technology Support for Agriculture (TSA) have insufficient explanatory power on average for GLUEAL. Agricultural Economic Development Level (AEDL), Urbanization Level (UL), Multiple Crop Index (MCI), Planting Structure (PS), Degree of Crop Damage (DCD), Financial support for agriculture (FSA), and Agricultural mechanization level (AML) had stronger explanatory power on average for GLUEAL and were important factors influencing GLUEAL levels. (4) The average influence of AEDL, UL, FSA, and AML on GLUEAL changed from negative to positive. The average influence of MCI and DCD on GLUEAL was negative, and the average influence of PS on GLUEAL changed from positive to negative. This study provides a comprehensive description of the spatial and temporal evolution of GLUEAL in China. It reveals the key factors influencing GLUEAL and analyzes their spatial variations and impact patterns. These findings offer robust evidence for government policymakers to formulate policy measures for sustainable agricultural development and optimized resource allocation, promoting the transformation of agricultural land towards green and low-carbon practices and advancing the achievement of sustainable development goals.

Cottonseed meal derived porous carbon prepared via the protease pretreatment and reduced activator dosage carbonization for supercapacitor.

The high catalytic activity and specificity of enzymes can be used to pretreat biomass. Herein, the resourceful, reproducible, cheap, and crude protein-rich cottonseed meal (CM) is selected as a precursor and the protease in the K2CO3-KHCO3 buffer solution is used as the enzyme degradation substance to pretreat CM. The crude protein content is significantly reduced by the protease degradation, and, meanwhile, it results in a looser and porous structure of CM. What is more, it significantly reduces the amount of activator. In the subsequent carbonization process, the K2CO3-KHCO3 in the buffer solution is also used as an activating agent (the mass ratio of CM to activator is 2:1), and after carbonization, the O, S, and N doped porous carbon is obtained. The optimized PCM-800-4 exhibits high heteroatom contents and a hierarchical porous structure. The specific capacitance of the prepared porous carbon reaches up to 233 F g-1 in 6M KOH even when 10 mg of active material is loaded. In addition, a K2CO3-KHCO3/EG based gel electrolyte is prepared and the fabricated flexible capacitor exhibits an energy density of 15.6 Wh kg-1 and a wide temperature range (-25 to 100 °C). This study presents a simple enzymatic degradation and reduced activator dosage strategy to prepare a cottonseed meal derived carbon material and looks forward to preparing porous carbon using other biomass.

Guide Positioning Sequencing identifies aberrant DNA methylation patterns that alter cell identity and tumor-immune surveillance networks.

Aberrant DNA methylation is a distinguishing feature of cancer. Yet, how methylation affects immune surveillance and tumor metastasis remains ambiguous. We introduce a novel method, Guide Positioning Sequencing (GPS), for precisely detecting whole-genome DNA methylation with cytosine coverage as high as 96% and unbiased coverage of GC-rich and repetitive regions. Systematic comparisons of GPS with whole-genome bisulfite sequencing (WGBS) found that methylation difference between gene body and promoter is an effective predictor of gene expression with a correlation coefficient of 0.67 (GPS) versus 0.33 (WGBS). Moreover, Methylation Boundary Shift (MBS) in promoters or enhancers is capable of modulating expression of genes associated with immunity and tumor metabolism. Furthermore, aberrant DNA methylation results in tissue-specific enhancer switching, which is responsible for altering cell identity during liver cancer development. Altogether, we demonstrate that GPS is a powerful tool with improved accuracy and efficiency over WGBS in simultaneously detecting genome-wide DNA methylation and genomic variation. Using GPS, we show that aberrant DNA methylation is associated with altering cell identity and immune surveillance networks, which may contribute to tumorigenesis and metastasis.

Angiotensin(1-7) Improves Islet Function in Diabetes Through Reducing JNK/Caspase-3 Signaling.

The aim of this study is to investigate whether Angiotensin (1-7), the physiological antagonist of Angiotensin II (AngII), has antidiabetic activity and the possible mechanism. Male Wistar rats were randomly divided into 3 groups: control group fed the normal diet, DM group fed high-fat diet and injected with STZ, and Angiotensin (1-7) group receiving injection of STZ followed by Angiotensin (1-7) treatment. Serum Ang II, fasting blood glucose, insulin, HOMA-IR, and HOMA-beta were determined in control, diabetes and Angiotensin (1-7) groups. The increased AngII and insulin resistance in diabetes group were accompanied by changes in islet histopathology. However, Angiotensin (1-7) improved the islet function and histopathology in diabetes without affecting the level of AngII. Western blot confirmed that Angiotensin (1-7) decreased the cleaved caspase 3 levels in pancreas of DM. The increased expression of JNK, Bax, and Bcl2 genes under diabetic conditions were partially reversed after Angiotensin (1-7) administration in pancreas. Immunofluorescence analysis showed that p-JNK was markedly increased in islet of DM rats, which was markedly alleviated after Angiotensin (1-7) treatment. Furthermore, Angiotensin (1-7) reversed high glucose(HG) induced mitochondrial apoptosis augments. Finally, Angiotensin (1-7) attenuated the apoptosis of INS-1 cells through reducing JNK activation in diabetes, which was blocked by anisomycin (a potent agonist of JNK). Our findings provide supporting evidence that Angiotensin (1-7) improved the islet beta-cells apoptosis by JNK-mediated mitochondrial dysfunction, which might be a novel target for the treatment and prevention of beta-cells dysfunction in DM.

Spiritual care perceptions and empathy of Chinese nursing students: The mediating roles of spiritual well-being.

OBJECTIVE: To investigate spiritual care perceptions, spiritual well-being, and empathy, examine the correlations among spiritual care perceptions, spiritual well-being, and empathy, and explore the mediating role of spiritual well-being between other two variables of Chinese nursing students. METHODS: A cross-sectional design was implemented, and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Checklist was used to ensure quality reporting of the study. A cluster sample of 2,718 nursing students was selected from 7 universities and colleges in China. The demographic characteristics questionnaire, the Chinese Version of the Spiritual Care-Giving Scale (C-SCGS), the Spiritual Health Scale Short Form (SHS-SF), and the Jefferson Scale of Physician Empathy-Nursing Student (JSPE-NS) were used. Descriptive statistics, correlation, and process plug-in mediation effect analyses were used to analyze the data. RESULTS: The total score of spiritual care perceptions, spiritual well-being, and empathy were 173.83 ± 25.62, 98.74 ± 12.87, and 105.04 ± 21.34, respectively. Spiritual care perceptions were positively correlated with spiritual well-being (r = 0.617, p < 0.01) and empathy (r = 0.528, p < 0.01). And spiritual well-being played a partial mediating role between the other two variables (accounting for 28.1%). SIGNIFICANCE OF RESULTS: Spiritual care perceptions, spiritual well-being, and empathy were quite moderate, which need in improving. It is suggested that nursing educators pay attention to the spiritual care education of nursing students, perfect the spiritual care education system, and take targeted measures according to nursing students' individual personality traits and differences, improve their spiritual well-being and empathy in multiple ways, so as to improve their spiritual care perceptions and competence.

Cell identity bookmarking through heterogeneous chromatin landscape maintenance during the cell cycle.

Genetic and epigenetic information are faithfully duplicated and accurately transmitted to daughter cells to preserve cell identity during the cell cycle. However, how the chromatin-based epigenetic information beyond DNA sequence is stably transmitted along with the disruption and re-establishment of chromatin structure within a cell cycle remains largely unexplored. Through comprehensive analysis DNA methylation and nucleosome positioning patterns of HepG2 cells in G0/G1, early S, late S and G2/M phases, we found that DNA methylation may act as the prime element for epigenetic inheritance after replication, as DNA methylation was extremely stable in each cell cycle phase, while nucleosome occupancy showed notable phase dependent fluctuation. Nucleosome-Secured Regions (NSRs) occupied by polycomb-repressed chromatin played a role in repressing the irrelevant cell type-specific genes and were essential for preventing irrelevant transcription factors binding, while the well-defined Nucleosome-Depleted Regions (NDRs) marked the genes crucial for cell identity maintenance. Chromatin structure at NSRs and NDRs was well maintained throughout the cell cycle, which played crucial roles in steadily preserving the transcriptional identity of the cell to fulfill cell identity maintenance. Collectively, our results demonstrated that while chromatin architecture underwent dynamic changes during cell cycle progression, DNA methylation together with NSRs and NDRs were stable epigenetic elements that were required for faithful transmission to the daughter cell to accurately maintain cell identity during the cell cycle.

Multifacet echelle grating for intensity broadening on spectral plane fabricated by rotating ion-beam etching.

This paper describes a new type of multifacet echelle grating (MFEG) for use in an echelle spectrometer. This new type of echelle grating broadens the spectral distribution on the spectral plane. We built a geometric model of MFEG to analyze the influence of the blaze angle and number of facet shapes on the spectral evolution. A dual-facet echelle grating and a four-facet echelle grating with different parameters were fabricated by rotating ion-beam etching with a self-shadowing rotating mask, based on the existing single-facet echelle grating (SFEG) with a line density of 52.7 g/mm and a blaze angle of 63.5°. The distributions of diffraction efficiency for different orders were measured with a He-Ne laser (632.8 nm); furthermore, these echelle gratings were applied in an echelle spectrometer (ICP-OES, Plasma2000), and testing spectra were obtained. The experimental results demonstrate that the MFEG can broaden the intensity distribution on the spectral plane, overcoming the weak spectral margin signal of SFEG spectrometers.

MBD3L2 promotes Tet2 enzymatic activity for mediating 5-methylcytosine oxidation.

Ten-eleven translocation (Tet) proteins are key players involved in the dynamic regulation of cytosine methylation and demethylation. Inactivating mutations of Tet2 are frequently found in human malignancies, highlighting the essential role of Tet2 in cellular transformation. However, the factors that control Tet enzymatic activity remain largely unknown. Here, we found that methyl-CpG-binding domain protein 3 (MBD3) and its homolog MBD3-like 2 (MBD3L2) can specifically modulate the enzymatic activity of Tet2 protein, but not Tet1 and Tet3 proteins, in converting 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). Moreover, MBD3L2 is more effective than MBD3 in promoting Tet2 enzymatic activity through strengthening the binding affinity between Tet2 and the methylated DNA target. Further analysis revealed pronounced decreases in 5mC levels at MBD3L2 and Tet2 co-occupied genomic regions, most of which are promoter elements associated with either cancer-related genes or genes involved in the regulation of cellular metabolic processes. Our data add new insights into the regulation of Tet2 activity by MBD3 and MBD3L2, and into how that affects Tet2-mediated modulation of its target genes in cancer development. Thus, they have important applications in understanding how dysregulation of Tet2 might contribute to human malignancy.

MicroRNAs activate gene transcription epigenetically as an enhancer trigger.

MicroRNAs (miRNAs) are small non-coding RNAs that function as negative gene expression regulators. Emerging evidence shows that, except for function in the cytoplasm, miRNAs are also present in the nucleus. However, the functional significance of nuclear miRNAs remains largely undetermined. By screening miRNA database, we have identified a subset of miRNA that functions as enhancer regulators. Here, we found a set of miRNAs show gene-activation function. We focused on miR-24-1 and found that this miRNA unconventionally activates gene transcription by targeting enhancers. Consistently, the activation was completely abolished when the enhancer sequence was deleted by TALEN. Furthermore, we found that miR-24-1 activates enhancer RNA (eRNA) expression, alters histone modification, and increases the enrichment of p300 and RNA Pol II at the enhancer locus. Our results demonstrate a novel mechanism of miRNA as an enhancer trigger.

Gonadal transcriptomic analysis of yellow catfish (Pelteobagrus fulvidraco): identification of sex-related genes and genetic markers.

Yellow catfish (Pelteobagrus fulvidraco) has been recognized as a vital freshwater aquaculture species in East and Southeast Asia. In addition to its commercial interest, it is also attracted much attention because of its value in studying sex-determination mechanisms. A comprehensive gonadal transcriptome analysis is believed to provide a resource for genome annotation, candidate gene identification, and molecular marker development. Herein, we performed a de novo assembly of yellow catfish gonad transcriptome by high-throughput Illumina sequencing. A total of 82,123 contigs were obtained, ranging from 351 to 21,268 bp, and N50 of 2,329 bp. Unigenes of 21,869 in total were identified. Of these, 229 and 1,188 genes were found to be specifically expressed in XY gonad tissue for 1 yr and 2 yr old yellow catfish, respectively; correspondingly, 51 and 40 genes were identified in XX gonad tissue at those two stages. Gene ontology and KEGG analysis were conducted and classified all contigs into different categories. A large number of unigenes involved in sex determination were identified, as well as microsatellites and SNP variants. The expression patterns of sex-related genes were then validated by quantitative real-time PCR (qRT-PCR) suggesting the high reliability of RNA-Seq results. In this study, the transcriptome of yellow catfish gonad was first sequenced, assembled, and characterized; it provides a valuable genomic resource for better understanding of yellow catfish sex determination as well as development of molecular markers, thereby assisting in the production of monosex yellow catfish for aquaculture.

Effect of metformin on serum interleukin-6 levels in polycystic ovary syndrome: a systematic review.

BACKGROUND: Most women with polycystic ovary syndrome (PCOS) have insulin resistance, hyperinsulinemia, and elevated serum IL-6 levels. These elevated IL-6 levels may have links with insulin resistance and hyperandrogenism. Metformin may have beneficial effects on the chronic low-grade inflammatory background associated with PCOS. METHODS: A systematic review was performed via PUBMED, EMBASE, and The Cochrane Library on PCOS studies published through November 30, 2013. Studies were selected that evaluated the effect of metformin on IL-6 levels in PCOS patients. Studies not containing adequate diagnosis information about PCOS or not excluding of other causes of hyperandrogenism were excluded. RESULTS: Five studies met the inclusion criteria. Of these, one study reported a significant decrease in IL-6 levels after metformin treatment in women with PCOS. Two studies reported that treatment-related reductions in IL-6 levels were significantly correlated with insulin metabolism. In the remaining two studies, plasma IL-6 levels did not change following metformin treatment. CONCLUSIONS: Serum IL-6 levels of PCOS patients may be influenced by metformin. Early application of metformin therapy may relieve chronic low-grade inflammation in women with PCOS. However, further investigations with larger samples are needed to better understand the effects of metformin on IL-6 levels and chronic inflammation in PCOS.

Chitosan combined with molecular beacon for mir-155 detection and imaging in lung cancer.

Lung cancer is the major cause of cancer-related deaths worldwide, thus developing effective methods for its early diagnosis is urgently needed. In recent years, microRNAs (miRNAs, miR) have been reported to play important roles in carcinogenesis and have become potential biomarkers for cancer diagnosis and treatment. Molecular beacon (MB) technology is a universal technology to detect DNA/RNA expression in living cells. As a natural polymers, chitosan (CS) nanoparticles could be used as a carrier for safe delivery of nucleic acid. In this study, we developed a probe using nanoparticles of miR-155 MB self assembled with CS (CS-miR-155 MB) to image the expression of miR-155 in cancer cells. Hybridization assay showed that the locked nucleic acid (LAN) modified miR-155 MB could target miR-155 effectively and sensitively. The miR-155 MB self-assembly with CS nanoparticles formed stable complexes at the proper weight ratio. The CS nanoparticles showed higher fluorescence intensity and transfection efficiency than the lipid-based formulation transfection agent by confocal microscopy and flow cytometry analysis. The CS-MB complexes were found to be easily synthesized and exhibited strong enzymatic stability, efficient cellular uptake, high target selectivity and biocompatibility. The CS-MB complexes can also be applied in other cancers just by simply changing for a targeted miRNA highly expressed in those cancer cells. Therefore, it is a promising vehicle used for detecting miRNA expression in living cells.

Multimodal diagnostic strategies and precision medicine in mucinous ovarian carcinoma: a comprehensive approach.

Mucinous ovarian carcinoma (MOC) represents a distinct entity within ovarian malignancies, characterized by diagnostic challenges due to its rarity and the potential overlap with other tumor types. The determination of tumor origin is important for precise postsurgical treatment. This article highlights the accurate diagnosis and management of MOC, including the use of imaging modalities, serological tumor markers, immunohistochemistry, and genomic analyses. Transabdominal and transvaginal ultrasonography, complemented by MRI and CT, plays a pivotal role in differentiating MOC from other mucinous tumors and in surgical planning, particularly for fertility preservation. Serological markers like CA19-9, CA-125, and CEA, though not definitive, provide valuable preoperative insights. Immunohistochemistry aids in distinguishing primary MOC from metastatic mucinous carcinomas, while genomic profiling offers the potential for precision medicine through the identification of specific molecular signatures and treatment susceptibilities. Despite advancements in diagnostic techniques, no single method conclusively differentiates between primary and metastatic tumors intraoperatively. The paper reviews the origins, diagnosis, and differential diagnosis of primary mucinous ovarian carcinoma highlights the need for a multimodal diagnostic approach and advocates for the inclusion of MOC patients in clinical trials for personalized therapies, recognizing the heterogeneity of the disease at the molecular level.

Cannabinoids improve mitochondrial function in skeletal muscle of exhaustive exercise training rats by inhibiting mitophagy through the PINK1/PARKIN and BNIP3 pathways.

Cannabidiol (CBD) is a pure natural phytocannabinoid derived from cannabis that has anti-inflammatory, antiapoptotic and antioxidative stress abilities. In recent years, an increasing number of studies have reported the regulatory effect of CBD on skeletal muscle injury induced by exercise, but its mechanism is still unclear. Mitochondria are the main organelles responsible for the energy supply within eukaryotic cells, and their function has been closely linked to cellular health. Moderate exercise improves mitochondrial function, but the excessive exercise has a negative impact on mitochondria. Therefore, we speculate that CBD may promote exercise induced skeletal muscle cell damage by improving mitochondrial function. In this study, by establishing an animal model of exhaustive exercise training in rats, the protective effect of CBD on skeletal muscle mitochondrial structure and function was elaborated, and the possible molecular mechanism was discussed based on transcriptomics. Our results indicate that skeletal muscle mitochondrial structure and function were improved after CBD intervention. GO and KEGG pathway enrichment analysis showed that exhaustive exercise training induced mitochondrial dysfunction in skeletal muscle is associated with excessive autophagy/mitophagy, the signaling pathways involved in FOXO3 and GABARAPL1 may play important roles. After CBD intervention, the protein expression of PINK1, PARKIN and BNIP3 was down-regulated, indicating that CBD may improve the mitochondrial function by inhibiting mitophagy through the PINK1/PARKIN and BNIP3 pathway.

Evaluation of nucleotide MALDI-TOF-MS for the identification of Mycobacterium species.

Background: The accurate identification of the Mycobacterium tuberculosis complex (MTBC) and different nontuberculous mycobacteria (NTM) species is crucial for the timely diagnosis of NTM infections and for reducing poor prognoses. Nucleotide matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) has been extensively used for microbial identification with high accuracy and throughput. However, its efficacy for Mycobacterium species identification has been less studied. The objective of this study was to evaluate the performance of nucleotide MALDI-TOF-MS for Mycobacterium species identification. Methods: A total of 933 clinical Mycobacterium isolates were preliminarily identified as NTM by the MPB64 test. These isolates were identified by nucleotide MALDI-TOF-MS and Sanger sequencing. The performance of nucleotide MALDI-TOF MS for identifying various Mycobacterium species was analyzed based on Sanger sequencing as the gold standard. Results: The total correct detection rate of all 933 clinical Mycobacterium isolates using nucleotide MALDI-TOF-MS was 91.64% (855/933), and mixed infections were detected in 18.65% (174/933) of the samples. The correct detection rates for Mycobacterium intracellulare, Mycobacterium abscessus, Mycobacterium kansasii, Mycobacterium avium, MTBC, Mycobacterium gordonae, and Mycobacterium massiliense were 99.32% (585/589), 100% (86/86), 98.46% (64/65), 94.59% (35/37), 100.00% (34/34), 95.65% (22/23), and 100% (19/19), respectively. For the identification of the MTBC, M. intracellulare, M. abscessus, M. kansasii, M. avium, M. gordonae, and M. massiliense, nucleotide MALDI-TOF-MS and Sanger sequencing results were in good agreement (k > 0.7). Conclusion: In conclusion, nucleotide MALDI-TOF-MS is a promising approach for identifying MTBC and the most common clinical NTM species.

Collagen synthase P4HA3 as a novel biomarker for colorectal cancer correlates with prognosis and immune infiltration.

Objective: In this study, we aimed to determine whether proly4-hydroxylase-III (P4HA3) could be used as a biomarker for the diagnosis of colorectal cancer (CRC) as well as for determining prognosis. Methods: We used The Cancer Genome Atlas (TCGA) database to analyze P4HA3 expression in CRC and further investigated the association between P4HA3 and clinicopathological parameters, immune infiltration, and prognosis of patients with CRC. Enrichment analysis was conducted to investigate the potential biological role of P4HA3 in CRC. To verify the results of TCGA analysis, we performed immunohistochemical staining of 180 clinical CRC tissue samples to probe into the relationship of P4HA3 expression with lymphocyte infiltration and immune checkpoints expression. Results: The expression of P4HA3 was significantly higher in CRC tissues and associated with a higher degree of malignancy and poorer prognosis in CRC. The results of enrichment analysis indicated that P4HA3 may be associated with the epithelial-mesenchymal transition process and the immune response. Immunohistochemical staining results showed that high P4HA3 expression was associated with high infiltration levels of CD8+ and Foxp3+ TILs and high PD-1/PD- L1 expression. Lastly, patients with CRC co-expressing P4HA3 and PD-1 had a significantly worse prognosis. Conclusion: High expression of P4HA3 is associated with adverse clinical features and immune cell infiltration in CRC, and has the potential to serve as a biomarker for predicting CRC prognosis.

ß-Mangostin targets and suppresses glioma via STING activation and tumor-associated microglia polarization.

Glioma, a common and highly malignant central nervous system tumor, markedly influences patient prognosis via interactions with glioma-associated macrophages. Previous research has revealed the anticancer potential of ß-mangostin, a xanthone derivative obtained from the mangosteen fruit. This research investigated the role of ß-mangostin on microglia in the glioma microenvironment and evaluated the efficacy of ß-mangostin combined with anti-PD-1 antibody (αPD-1) in glioma-bearing mice. The results showed that, ß-mangostin attenuated M2 polarization in BV2 cells and promoted M1-related interleukin (IL)-1ß and IL-6 secretion, thereby inhibiting glioma invasion. In addition, ß-mangostin improved the anti-glioma effects of αPD-1 and increased CD8+T cell and M1-type microglia infiltration. Mechanistically, ß-mangostin bound to the stimulator of interferon genes (STING) protein, which is crucial for the anti-tumor innate immune response, and promoted STING phosphorylation in microglia, both in vivo and in vitro. These results provide insights into its mode of action and supporting further investigation into ß-mangostin as a therapeutic agent.

miR-1246 promotes osteosarcoma cell migration via NamiRNA-enhancer network dependent on Argonaute 2.

High metastatic propensity of osteosarcoma leads to its therapeutic failure and poor prognosis. Although nuclear activation miRNAs (NamiRNAs) are reported to activate gene transcription via targeting enhancer and further promote tumor metastasis, it remains uncertain whether NamiRNAs regulate osteosarcoma metastasis and their exact mechanism. Here, we found that extracellular vesicles of the malignant osteosarcoma cells (143B) remarkably increased the migratory abilities of MNNG cells representing the benign osteosarcoma cells by two folds, which attributed to their high miR-1246 levels. Specially, miR-1246 located in nucleus could activate the migration gene expression (such as MMP1) to accelerate MNNG cell migration through elevating the enhancer activities via increasing H3K27ac enrichment. Instead, MMP1 expression was dramatically inhibited after Argonaute 2 (AGO2) knockdown. Notably, in vitro assays demonstrated that AGO2 recognized the hybrids of miR-1246 and its enhancer DNA via PAZ domains to prevent their degradation from RNase H and these protective roles of AGO2 may favor the gene activation by miR-1246 in vivo. Collectively, our findings suggest that miR-1246 could facilitate osteosarcoma metastasis through interacting with enhancer to activate gene expression dependent on AGO2, highlighting the nuclear AGO2 as a guardian for NamiRNA-targeted gene activation and the potential of miR-1246 for osteosarcoma metastasis therapy.

[Effects of carnitine on respiratory chain and metabolism of oxygen radical in mitochondria of skeletal muscle after exhaustive running in training rat].

The aim of the present study was to investigate the effect of carnitine on function of respiratory chain and metabolism of oxygen radical in mitochondria of skeletal muscle after exhaustive running in training rats. Forty male Wistar rats were randomly divided into 4 groups (n = 10): control, carnitine, training and training + carnitine groups. The training and training + carnitine groups received 6-week treadmill training, whereas carnitine and training + carnitine groups were administered intragastrically with carnitine (300 mg/kg per day, 6 d/week) for 6 weeks. After exhaustive running, all the rats from 4 groups were sacrificed to obtain quadriceps muscles samples, and muscle mitochondria were extracted by differential centrifugation. Spectrophotometric analysis was used to evaluate activities of respiratory chain complexes (RCC) I-IV, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the content of malondialdehyde (MDA) in the skeletal muscle mitochondria. The results showed that, compared with the control group, the carnitine group exhibited increased RCCI and RCCIII activities (P < 0.05), the training + carnitine group exhibited increased RCCI, RCCIII and RCCIV activities (P < 0.05 or 0.01). Moreover, RCCIII activity in the training + carnitine group was higher than that in training group (P < 0.05). Compared with the control group, the carnitine, training and training + carnitine groups showed increased SOD activities ( P < 0.01), the carnitine and training + carnitine groups showed increased GSH-Px activities ( P < 0.01), the carnitine, training and training + carnitine groups showed increased MDA contents (P < 0.05 or 0.01). The SOD and GSH-Px activities in training + carnitine group were higher than those in training group (P < 0.01), and the MDA level in the training + carnitine group was higher than that in the carnitine and training groups (P < 0.01). These results suggest that training and carnitine can increase function of respiratory chain, antioxidation and lipid peroxidation tolerance capacity in skeletal muscle mitochondria, and the improving effects of training and carnitine are synergistic.